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Tyrosine phosphorylation of VHR phosphatase by ZAP-70

Nature Immunologyvolume 4pages4448 (2003) | Download Citation

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Abstract

The ZAP-70 tyrosine kinase is a key component of the signaling machinery for the T cell antigen receptor (TCR). Whereas recruitment and activation of ZAP-70 are relatively well understood, the proteins phosphorylated by ZAP-70 are incompletely known. We report here that VHR, a Vaccinia virus VH1-related dual-specific protein phosphatase that inactivates the mitogen-activated kinases Erk2 and Jnk, is phosphorylated at Y138 by ZAP-70. Tyr138 phosphorylation was required for VHR to inhibit the Erk2–Elk-1 pathway and, conversely, the VHRY138F mutant augmented TCR-induced Erk2 kinase and activation of the gene encoding interleukin 2. These results suggest that VHR is a target for ZAP-70 and tempers activation of the Erk2 pathway in a ZAP-70–controlled manner.

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Acknowledgements

We thank P. King for the MKP6 cDNA and B. Moss for the VH1 plasmid. Supported by the Spanish Ministry of Education and Culture, Rotary International, Van Beirs Foundation, Centre Anticancéreux près L'Université de Liège and by grants AI35603, AI40552 and AI48032 from the National Institutes of Health.

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Affiliations

  1. Program of Signal Transduction, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, 92037, CA, USA

    • Andres Alonso
    • , Souad Rahmouni
    • , Scott Williams
    • , Robert T. Abraham
    •  & Tomas Mustelin
  2. La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, 92121, CA, USA

    • Marianne van Stipdonk
    •  & Stephen P. Schoenberger
  3. Bioinformatics, Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, 92037, CA, USA

    • Lukasz Jaroszewski
    •  & Adam Godzik

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The authors declare no competing financial interests.

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Correspondence to Tomas Mustelin.

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https://doi.org/10.1038/ni856

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